Iranian Journal of Pharmaceutical Research
Volume:9 Issue: 4, Autumn 2010

Nanotechnology, shortened to nanotech, is the study of the controlling of matter on an atomic and molecular scale. Generally, nanotechnology deals with structures sized between 1 to 100 nanometer in at least one dimension and involves developing materials or devices within that size. The use of nanotechnology in the field of pharmaceutics and drug delivery has grown over the last few years, so remarkably that the pharmaceuticals developed on the basis of this technology are termed as Nanopharmaceuticals. Among the nanopharmaceuticals currently being used or under investigation, one can mention nanoemulsions, nanosuspensions, nanospheres, carbon nanotubes, micellar nanocarriers (polymeric micelles), nanocapsules, lipid nanoparticles, self-nanoemulsifying systems, dendrimers, etc.

Clopidogrel, an inhibitor of platelet aggregation, selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Oral bioavailability of clopidogrel is very low (less than 50%), due to its poor water solubility. The aim of this investigation was to design and develop a microemulsion formulation of clopidogrel for enhancing its solubility, and hence its oral bioavailability. For this purpose, initially, solubility of clopidogrel was determined in various vehicles. Next, pseudo-ternary phase diagrams were constructed to identify the microemulsion existing zone. Solubility study was also performed for optimization of formulation. The optimized microemulsion formulation was characterized for its transparency, droplet size, zeta potential, viscosity, conductivity, % assay, and phase separation study. Particle size and zeta potential of the optimized microemulsion formulation were found to be 12.3 nm, and -6.34 mV, respectively. The viscosity and conductivity data indicated that the microemulsion was of the o/w type. Solubility of clopidogrel was successfully enhanced by 80.66 times, via capmul microemulsion, compared with distilled water (pH = 7.4). 75.53% and 71.2 % of the drug content were found to be released within 9 h in the in-vitro and ex-vivo studies, respectively. Hence, by formulating into microemulsion, the solubility of clopidogrel was found to be significantly enhanced.

The aim of this study was to design orally disintegrating tablets of Olanzapine and to complex Olanzapine with 2-hydroxypropyl-β- cyclodextrin with special emphasis on disintegration and dissolution studies. Phase solubility studies demonstrated the formation of 1:1 molar inclusion complex by kneading method. Tablets were prepared by using superdisintegrants namely, sodium starch glycolate, croscarmellose sodium, crospovidone, tulsion 339, and indion 414. Complex was characterized using infrared spectroscopy, drug content estimation, saturated solubility study, diffrerential scanning calorimetry and X-ray diffractometry. 5% w/w croscarmellose sodium showed the minimum disintegration time 39 ± 1.76 sec and in-vitro drug release 99.19 ± 0.18% within 6 min. In general, solubility of Olanzapine can be improved by complexing with 2-hydroxypropyl-β- cyclodextrin. Croscarmellose sodium can be used for faster disintegration of tablets.

This paper reviews the use of texture analysis in studying the performance of hydrophilic matrices of highly soluble drugs and different types of excipients (i.e. water-soluble, water-insoluble and swellable, and water insoluble and non-swellable). Tablets were prepared by direct compression, and their swelling and erosion in presence of these different excipients were assessed with the help of volumetric, gravimetric, morphological, and rheological studies. Dissolution test was performed using USP 26 apparatus 2 modified by insertion of a sieve to prevent sticking of the tablets to the bottom of the vessel and allow them to swell 3-dimensionally. Loading 15% of the highly soluble drug in formulations containing 65% lactose showed the most pronounced swelling and erosion and the best sustained drug release, compared to matrices containing microcrystalline cellulose and dicalcium phosphate. The correlation between front movement, mass erosion and solute transport in relation to excipient type on progression of probe displacement and total work was examined throughout texture analysis studies. The formulation containing the soluble excipient lactose showed better swelling and erosion properties compared to formulations containing the swellable and insoluble excipients. In conclusion, it could be said that based on the distinct conventional dosage forms insertion of particular excipients in hydrophilic controlled release tablets containing water soluble drug, the finger print information of drug release profile could be obtained. To study the release profile from hydroxy propyl methyl cellulose K 15M matrices with different types of excpients, diltiazem hydrochloride was used as a model soluble drug.

The present study deals with development of a floating in-situ gel of the narrow absorption window drug baclofen. Sodium alginate-based in-situ gelling systems were prepared by dissolving various concentrations of sodium alginate in deionized water, to which varying concentrations of drug and calcium bicarbonate were added. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to check the presence of any interaction between the drug and the excipients. A 32 full factorial design was used for optimization. The concentrations of sodium alginate (X1) and calcium bicarbonate (X2) were selected as the independent variables. The amount of the drug released after 1 h (Q1) and 10 h (Q10) and the viscosity of the solution were selected as the dependent variables. The gels were studied for their viscosity, in-vitro buoyancy and drug release. Contour plots were drawn for each dependent variable and check-point batches were prepared in order to get desirable release profiles. The drug release profiles were fitted into different kinetic models. The floating lag time and floating time found to be 2 min and 12 h respectively. A decreasing trend in drug release was observed with increasing concentrations of CaCO3. The computed values of Q1 and Q10 for the check-point batch were 25% and 86% respectively, compared to the experimental values of 27.1% and 88.34%. The similarity factor (f2) for the check-point batch being 80.25 showed that the two dissolution profiles were similar. The drug release from the in-situ gel follows the Higuchi model, which indicates a diffusion-controlled release. A stomach specific in-situ gel of baclofen could be prepared using floating mechanism to increase the residence time of the drug in stomach and thereby increase the absorption.

Triptoreline is a potent agonist of luteinizing hormone-releasing hormone, currently used in the treatment of prostatic cancer where therapy may be required over months or years. Frequent injection of drug decreases patients’ compliance. The present study describes the formulation of a sustained release microparticulate drug delivery system containing triptoreline acetate, using poly (D,L lactide-co-glycolide) (PLGA). Biodegradable microspheres were prepared using 50: 50 PLGA by a water in-oil-in-water (w/o/w) double emulsion-solvent evaporation procedure and characterized for drug content and drug release rate using the a HPLC method, particle size distribution using the laser diffraction method, and surface morphology using scanning electron microscopy and drug release rate. Effect of critical process parameters and formulation variables; i.e. volume of inner water phase, addition of NaCl to the outer aqueous phase (W2), addition of different types and amounts of emulsifying agents on microsphere characteristics; were investigated. Microspheres prepared were spherical with a smooth surface, but addition of poloxamer to the first emulsion produced microspheres with large pores. Size of microparticles was dependent on the type, as well as the amount of co-encapsulated surfactants. Increasing the inner water phase volume resulted in larger particles with a lower encapsulation efficiency. Low concentrations of Span 20 decreased triptoreline release rate, whereas the addition of poloxamer or high concentrations of Span 20 increased the drug release rateit. In conclusion, by selecting an appropriate level of the investigated parameters, spherical microparticles with encapsulation efficiencies higher than 90% and a prolonged triptoreline release over 45 days were obtained.

Phencyclidine (1-(1-phenylcyclohexyl) piperidine, PCP, I) and ketamine (2-O-chlorophenyl-2-methylaminocyclohexan, II) have shown analgesic effects. Some of its derivatives were synthesized and their biological properties have been studied. In this study, a new derivative of PCP, (1-[1-(3-methoxyphenyl) (tetralyl)] piperidine, PCP-OCH3-tetralyl, III) was synthesized and the acute thermal pain of this compound was determined using tail immersion test on rats and the results were compared with Ketamine and PCP. The results indicated a marked anti-nociception 2-25 min after ketamine injection, but the analgesic effect remained for 40 min following PCP-OCH3-tetralyl application in tail immersion test. However, the data obtained from formalin test showed that the chronic anti-nociception effect of ketamine was higher than PCP and PCP-OCH3-tetralyl exhibited almost similar analgesic effect.

A substantial amount of evidence has proposed an important role for Cyclooxygenase-2 (COX-2) enzyme in brain diseases and affiliate disorders. The purpose of this research was studying the effects of COX-2 selective inhibition on haloperidol-induced catatonia in an animal model of drug overdose and Parkinson’s disease (PD). In this study, the effect of acute and Sub-chronic oral administration of a new selective COX-2 inhibitor, i.e. the compound 11b or 1-(Phenyl)-5-(4-methylsulfonylphenyl)-2-ethylthioimidazole, in a dosage of 2, 4 and 8 mg/kg on haloperidol-induced catatonia was evaluated and compared to the standard drug scopolamine (1 mg/kg) by microanalysis of Striatum dopaminergic neurotransmission. The results showed a very high potency for 11b in improving the catalepsy by enhancing the dopaminergic neurotranmission (p < 0.05). In addition, statistical analysis showed the dose- and time-dependent behavior of the observed protective effect of 11b against the haloperidol-induced catatonia and enhancement of the dopaminergic neurotransmission. These findings are additional pharmacological data that suggest the effectiveness of COX-2 inhibition in treatment of schizophreny-associated rigidity.

Teucrium polium (Labiatae) is a plant that widely grows in Iran. Some of species of Teucrium are used for a considerable range of actions in traditional medicine and T. polium has frequently been used as anticonvulsant. In this study, we investigated the protective effects of T. polium ethanolic aqueous extracts and related fractions on seizures induced by pentylenetetrazole (PTZ) and maximal electroshock stimulation (MES). Moreover, presence of alkaloids, terpenoids, tannins and flavonoid contents were evaluated. It was found that aqueous extract (ED50 = 22.4 mg/kg body weight) and related n-butanol fraction (ED50 = 12.6 mg/kg body weight) have antiseizure effects comparing to control groups. There was no difference between preventing of PTZ-induced death and MES-induced hindlimb tonic extension (HLTE) in ethanolic extract comparing to control groups. Our results showed that the amount of flavonoid quantity present in aqueous extract is higher than that of ethanolic extract. These data also showed that the quantity of the flavonoid in n-butanol fraction of aqueous extract is more than other fractions. In conclusion, it was realized that flavonoid rich extracts are more potent than other fractions in showing antiseizure effects.

There are considerable efforts to identify naturally occurring substances as new drugs in cancer therapy. Many components of medicinal plants have been identified that possess substantial anticancerous properties. This prompted us to investigate the effect of Scrophularia striata (an Iranian species belonging to the Scrophulariace family) extract on the growth of astrocyte cancer cell line (1321). The 1321 cell line were seeded in 96-well culture plates in the presence and absence of various concentrations of either leaf and seed filtered and unfiltered extract of Scrophularia striata to determine their probable anticancer effects in comparison with etoposide (chemical anticancer reagent). filtered leaf extract of S. Striata showed strong anticancer effect on 1321cell line as compared to control group (cells not exposed to extracts), and even the group (adenocarcinoma gastric cell line) exposed to etoposide. Unlike the leaf extract, the seed extract activated cell proliferation in all experiments. Flow cytometry findings indicated that apoptosis is the mechanism by which the leaf extract inhibits cell proliferation. Our findings indicate that both leaves and seeds of S. Striata contain both anti cancer and cell growth enhancing agents.

Brown alga, Turbinaria conoides was successively extracted with n-hexane, cyclohexane, methanol and ethanol:water (1:1). The extracts were evaluated for antibacterial and antifungal activities by disc diffusion method. Minimal inhibitory concentration was determined for active extracts by broth dilution method. The antiviral activity and cytotoxicity of the extracts were tested in human embryonic lung (HEL) cells (herpes simplex virus-1, herpes simplex virus-2, vaccinia virus, vesicular stomatitis virus and herpes simplex virus-1 TK- KOS ACVr), human epithelial (HeLa) cells (vesicular stomatitis virus and coxsackie virus B4) and Vero cells (parainfluenza-3 virus, reovirus-1, sindbis virus coxsackie virus B4 and punta toro virus). The results revealed that extracts exhibited cytotoxicity ranged from 20 to >100 µg/mL. Moderate activity was demonstrated by n-hexane and cyclohexane extracts against viruses, whereas methanol and ethanol:water (1:1) extracts were not active. Ethanol:water (1:1) presented neither antibacterial nor antifungal activity against tested organisms. Cyclohexane extract possessed a broad array of antibacterial activity and exhibited remarkable antifungal property. It is noteworthy that minimal inhibitory concentration of cyclohexane extract against Aspergillus niger is comparable with that of clotrimazole. This potentiality demonstrates that it could be used to treat bacterial and fungal infections.

This study was designed to examine the chemical composition and in-vitro antioxidant activity of the essential oil and methanolic extract of Teucrium orientale subsp. taylori. The GC and GC–MS analysis of the essential oil resulted in determination of 40 components representing 96.4% of the oil. The major constituents of the oil were linalool (28.6%), caryophyllene oxide (15.6%), 1,8-cineol (4.5%), β-pinene (8.7%), 3-octanol (9.5%), β-caryophyllene (7.3%), and germacrene-D (4.1%). Antioxidant activities of the samples were determined by two different tests, namely DPPH and β-carotene- linoleic acid assay. In DPPH system, the weakest radical scavenging activity was exhibited by the non-polar sub fraction of methanolic extract (237.40 ± 2.1 μg/mL). Antioxidant activity of the polar sub fraction of methanolic extract was superior to all samples tested, showing an EC50 value of 61.45 ± 0.5 μg/ mL. The inhibition capacity (%) of the polar sub fraction of methanolic extract (95.21% ± 1.3) was found to be the strongest and almost equal to the inhibition capacity of the positive control BHT (94.9% ± 1.1). The amount of the total phenolics was the highest in the polar subfraction, i.e. 370 μg/mg of the dry extract (37%). A positive correlation was observed between the antioxidant activity and the total phenolics of the extracts.

Licorice (Glycyrrhiza glabra L.) is an important medicinal plant. In this study, the antimicrobial activities of ethanolic and aqueous extracts from licorice leaves were studied compared to root extracts activities. Bacillus subtilis, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli, and Candida albicans were used as test organisms. Antimicrobial activity was tested by paper disc agar diffusion and serial dilution methods in order to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The root and leave extracts showed activity against Candida albicans, and tested gram-positive bacteria in a dose dependent manner. The ethanolic extract of the leaves was the most active extract against gram-positive bacteria. Its effectiveness against strains provides hope that it can serve as an alternative therapeutic agent.

Fractions obtained from partitioning of aerial methanolic extract of Euphorbia Aellenii with chloroform (E2), ethyl acetate (E3), n-butanol (E4) and water (E5) were investigated in vitro for their phytotoxicity, insecticidal, anti-leishmanial, cytotoxicity, antibacterial and antifungal activities. Sample E2 appeared to have significant phytotoxic activity. In the insecticidal screening study only one of the insects, Rhyzopertha dominica, showed acceptable mortality after treatment with E2, but weak response to E3 and E4 fractions. Leishmanicidal activity of the chloroform fraction was present, but not very significant. E2 showed favorable cytotoxic activity, while E3 had weak activity, and the other samples had no significant activity. In the antifungal screening tests; E2, E3 and E4 fractions exhibited about 25% inhibition of fungal growth against Fusarium solani, while they were not active against other tested fungi. The results of antibacterial screening were completely negative, which may be due to resistance towards these types of constituents.

The purpose of this study was to determine the prevalence of anti-microbial resistance in intubated patients in intensive care unit (ICU) of Bahonar hospital in Kerman province, Iran during the year 2008. Tracheal samples were obtained from 111 intubated patients in the ICU by broncoalveolar lavage method. Amikacin, Ceftazidim and Imipenem were used to evaluate antibiotic susceptibility. For detecting anti-microbial susceptibility, minimum inhibitory concentration method were used. Colony counts equal or more than 104 microorganisms/mL were considered resistant. Overall we obtained positive tracheal cultures from 32 patients (29%) out of 111 intubated ones. The most common micro organisms isolated were Klebsiella (90.6%), Acinetobacter (28.1%) and Pseudomonas (21.9%). The results showed that the most common resistance was against to ceftazidim. The susceptibility of Klebsiella in tracheal cultures to the antibiotics was only 5%. E. coli in both sexes was 100% resistant to the tested antibiotics. In the ICU, There was a very big problem concerning antibiotic resistance. Most of the isolated microorganisms were resistant to both the old and the new antibiotics. It may be related to the inappropriate use of antibiotics, bacterial contamination of enteral feeding and infection transmission by medical staff or instruments.

Human milk contains all of the constituents that are required for the optimal growth and development of a neonate. It supports the development of brain, immune, and physiological systems. This study aimed to consider the significance of breast milk in preventing oxidative stress by comparing total antioxidant capacity (TAC) in breast and formula milk for premature infants, demonstrating the relationship between TAC in breast milk and postnatal age in days. The Ferric reducing antioxidant power assay (FRAP) method was used to spectophotometrically measure of TAC in breast and formula milk. One hundred and fourty (n = 140) lactating mothers agreed to participate in the study. TAC was also measured in two brands of formula milk (n = 80). The Range of TAC in human breast milk was 234.27-1442.31 µM and in two formula was 160.04-630.92 µM. The average TAC was significantly higher in breast milk (642.94 ± 241.23 µM) compared to formula milk (280.986 ± 100.34 µM) p < 0.0001. The TAC of breast milk was increased with some nutritional parameter such as increased consumption of cheese, vegetables, fruits, bread and nuts. Infants’ height at the birthday was directly correlated with antioxidant capacity of breast milk, whilst a reversed correlation was observed between TAC in breast milk and infant age. Based on our results, it is concluded that the TAC of breast milk is varied and affected by nutrition. It is alo observed that TAC is significantly higher in breast milk than formula, which means that breast milk provides better antioxidant potency than infant formula.

Although arterialovenous fistulae (AVF) is considered to be vital for chronic kidney disease (CKD) patients, but they may cause complications and problems. For instance they may fail soon after their creation. The most important cause of failure in these cases is intrafistula thrombus formation. Whereas anti-platelet drugs are not routinely used after fistulae creation, we conducted this study to determine the effect of these drugs (aspirin and dipyridamol) on the patency of AVFs. From Sep 2003 to Aug 2007, all CKD patients who needed AVF for hemodilysis were included in our study. After fistulae creation, they were randomly divided in 3 groups. The first group was received aspirin and the second one with dipyridamol and the third one was the control group that received placebo. Each group consisted of 130 patients. Exclusion criteria were bleeding tendency, active peptic ulcer disease, pregnancy, lactation, use of anticoagulant and or non steroidal anti-inflammatory drugs, hepatic insufficiency and history of significant side effects from aspirin or dipyridamol. The patency of AVF in the control, aspirin and dipyridamol groups were obtained 69.2%, 70.8% and 75.4% respectively. Although the patency in the aspirin and the dipyridamol group were 1.6% and 6.2% more than the control group, but there was no statistically significant difference between them and placebo (The p-value was 0.892 for the aspirin group and 0.332 for the dipyridamol group). Our study showed that neither the aspirin nor the dipyridamol can be effective on the patency of AVF after 72 h even within six months period.